Deoxycytidine kinase is an enzyme involved in deoxynucleoside salvage, supplying precursors for DNA synthesis. Csapó, Z. et al., Acta Biochimica Polonica 48(1):251-256, 251 (2001). The enzyme is able to phosphorylate three of the four deoxynucleosides, and also phosphorylates a variety of antineoplastic and antiviral nucleoside analogues. Id.; Chottiner, E. G., et al, Proc. Natl. Acad. Sci. USA 88:1531-1535, 1531 (1991). For example, the enzyme reportedly activates cytosineb-D-arabinofuranoside (AraC), fludarabine and cladribine, the chemotherapeutic agents gemcytabine and troxacitabine, and the antivirals 3TC and ddC, which are used in the treatment of HIV infection. Sabini, E. et al., Nature Stuct. Biol. 10(7):513-519, 513 (2003).
Although deoxycytidine kinase activates some anti-cancer drugs, reports suggest that at least one anti-cancer drug may act, at least in part, by inhibiting the enzyme. See, e.g., International Application WO04/103374. In this regard, a link between neoplastic transformation and increased deoxycytidine kinase levels in solid cancer tissues has been reported. See Arnér, E. S. J. and Eriksson, S., Pharmac. Ther. 67(2):155-186, 165 (1995). Some deoxycytidine kinase inhibitors have been reported. See, e.g., Krenitsky, T. A. et al., J. Biol. Chem. 251(13):4055-4061 (1976); Ward, A. D. and Baker, B. R., J. Med. Chem. 20(1):88-92 (1976).